PROPOSAL SUMMARY Since she arrived at The Albert Einstein College of Medicine in 2007, Dr. Blouet developed a novel research theme in Dr. Schwartz lab focusing on the role of brain amino acid sensing in the regulation of energy balance. During this time, the candidate proved her dedication to biomedical research in metabolic diseases and an outstanding potential for becoming a successful independent investigator. Her work led to landmark discoveries on the role of hypothalamic amino acid detection through p70 S6 kinase 1 (S6K) in the regulation of energy balance in rodents. During the K99 mentored phase of this proposal, Dr. Blouet will focus on her short-term career goals with specific research and training objectives. In collaboration with her mentor Dr. Schwartz, she will complete her current research assessing the role of the caudal brainstem dorso-vagal complex (DVC) in amino acid sensing and testing the hypothesis that DVC S6K is a critical mediator of central nutrient sensing and the regulation of energy homeostasis. To successfully complete this component of her research plan, the candidate will take advantage of the outstanding, state-of-the-art research and teaching environment available at The Albert Einstein College of Medicine. Specifically, she will advance her training in neuropharmacology, molecular genetics and electrophysiology and neuroanatomical tract tracing, under the guidance of her mentoring committee, composed of experts in each of these specialties, as well as engage in relevant coursework, research seminars and symposia, career development and grant writing workshops, and speaking opportunities at scientific meetings. The long-term career goals of this proposal are to enable the candidate to successfully launch her own research team, train fellows and students, establish new collaborations, and produce grant proposals to secure independent funding. To this end, career development activities during the K99 phase will give the candidate the keys to successfully launch her laboratory. During the R00 phase of this award, Dr. Blouet will develop her independent research program focused on the role of forebrain/hindbrain nutrient-sensing circuits in the regulation of energy balance in rodents, and assess a potential role for impaired central nutrient sensing in diet-induced obesity and metabolic dysfunction. Ultimately, this research will provide new insights onto the mechanisms underlying central nutrient sensing and the regulation of energy homeostasis.